Gemcitabine plus cisplatin versus gemcitabine as adjuvant therapy after curative-intent resection of cholangiocarcinoma (GeCiCCA): a multicenter, randomized controlled, phase III trial

Background: This randomized controlled trial aims to evaluate whether adjuvant gemcitabine plus cisplatin improves overall survival compared to gemcitabine monotherapy in patients with resected cholangiocarcinoma (CCA). Secondary outcomes include assessment of disease-free survival, treatment safety, and adherence. Methods: This phase III, multicenter, randomized controlled trial enrolled 80 patients with resected CCA, randomized to receive either gemcitabine plus cisplatin or gemcitabine monotherapy. Outcomes including overall survival, disease-free survival, and safety were assessed. Findings: At a median follow-up of 83.5 months (95% CI, 73.8–91.2), data were censored on 30 January 2025. A total of 45 deaths (56.3%) were documented. The median overall survival was 68.9 months in the gemcitabine–cisplatin group compared with 49.1 months in the gemcitabine group; however, the difference was not statistically significant (hazard ratio [HR], 0.87; 95% CI, 0.48–1.58; P = 0.655). Similarly, median DFS did not differ significantly between gemcitabine plus cisplatin (36.6 months) and gemcitabine alone (36.2 months) (HR, 0.87; 95% CI, 0.49–1.53; P = 0.625). Subgroup analyses showed non-significant trends favoring combination therapy in patients with intrahepatic tumors, lymph node-negative disease, and early-stage CCA. Treatment adherence was lower in the combination group than in the monotherapy group (62.5% vs. 92.5%). Grade 3–4 adverse events were more frequent with combination therapy (77.5% vs. 70%), with higher rates of nephrotoxicity and hepatotoxicity observed. Interpretation: Adjuvant gemcitabine plus cisplatin did not significantly improve OS or DFS compared to gemcitabine alone in resected CCA. Combination therapy was associated with higher toxicity and lower adherence.